Activation of GPR30 stimulates GTP-binding of G alpha i1 protein to sustain activation of Erk1/2 in inhibition of prostate cancer cell growth and modulates metastatic properties
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AbstractPreviously, we reported that GPR30 activation by the receptor-specific, non-estrogenic ligand G-1 inhibited in vitro and in vivo growth of prostate cancer (PCa) cells via sustained Erk1/2 activation. Mechanism underlying the sustained Erk1/2 activation for PCa cell growth inhibition remains unclear. Here we report that G-1, through GPR30, activated G alpha i1 proteins to sustain Erk1/2 activation but failed to activate adenylyl cyclase (AC) for cAMP production in PCa cells. The chemical-induced activation of AC-cAMP-PKA signaling attenuated Erk1/2 activity and blocked the cell growth inhibitory effects of G-1. Furthermore, PCa predominantly expressed G alpha i1 proteins. Silencing of G alpha i1 expression blocked the inhibitory effects of G-1 on PCa cell growth. By gene expression profiling, GPR30 activation by G-1 interfered expression of cell cycle regulators and machinery elements to modulate PCa cell growth and the RACGAP1 interactome to control metastatic properties. In this regard, we demonstrated that G-1 inhibited PCa cell migration and invasion with reduced formations of filopodia and stress fibers through a GPR30-dependent pathway. Taken together, our findings revealed the underlying mechanism for sustaining Erk1/2 activation upon GPR30 activation by G-1 in PCa cells and the GPR30-mediated pathways in controlling PCa cell growth and metastatic properties.
All Author(s) ListLau KM, Ma FMT, Xia JT, Chan QKY, Ng CF, To KF
Journal nameExperimental Cell Research
Year2017
Month1
Volume Number350
Issue Number1
PublisherELSEVIER INC
Pages199 - 209
ISSN0014-4827
eISSN1090-2422
LanguagesEnglish-United Kingdom
KeywordsGPER, G protein-coupled estrogen receptor, G-1, Migration, Invasion
Web of Science Subject CategoriesOncology;Cell Biology;Oncology;Cell Biology

Last updated on 2020-08-08 at 00:59